Inhalation therapy for delivering both locally/topically and systemically active drug compounds is increasing as the health-care community recognizes the benefits this route offers to patients. For some therapeutic agents, delivery of the aerosolized liquid without a propellant is preferred. Such liquids may be aerosolized, for example, by an electrohydrodynamic (EHD) apparatus. EHD aerosol delivery systems are expected to revolutionize inhalation therapy. These novel systems are more efficient and reproducible than existing inhalation devices. EHD devices can deliver a soft (isokinetic) cloud of uniformly sized particles directly to the lungs with better than 90 percent efficiency, and without the need for liquid propellants or other pressurized systems. The aerosol is delivered using the patient's own breath (inspiration), whereby the patient can easily achieve the drug delivery at normal inhalation rates. The delivery mechanism is especially suited to use with infants, young children, seniors, and patients with an impaired respiratory function.
A net electric charge is imparted to the fluid by putting a charged electrode in the fluid path. The liquid to be aerosolized is made to flow through a region of high electric field strength. This fluid charge tends to remain on the surface of the liquid such that, as the liquid exits the nozzle, the repelling force of the surface charge balances against the surface tension of the liquid, forming a cone (a “Taylor cone” as described in, e.g., M. Cloupeau and B. Prunet-Foch, “Electrohydrodynamic Spraying Functioning Modes: A Critical Review,” J Aerosol Sci., Vol. 25, No. 6, pp. 1021, 1025-1026 (1994)). In the region of the tip of the cone, which has the greatest charge concentration, the electrical force exerted on the liquid surface overcomes the surface tension, generating a thin jet of liquid. The jet breaks into droplets of more or less uniform size, which collectively form a cloud that may be inhaled by a user to deliver the aerosol to the user's lungs.
It is generally known to aerosolize pharmaceutical formulations and discharge the aerosol particles prior to their delivery to a user. One such method uses an electrohydrodynamic apparatus having a single spray site (nozzle tip) surrounded by discharge electrodes and a grounded shield to produce a monodispersed spectrum of particle sizes. Although these known approaches produce an aerosolized liquid, they have a number of disadvantages.
Generally known pulmonary delivery devices that use electrohydrodynamic spraying are unwieldy and require connection to either an alternating current power supply or a large direct current power supply. These conventional devices are suitable for use in hospital or other clinical applications, such as for administering a therapeutic agent during a scheduled treatment appointment, but generally are not suitable for use directly by a user on a demand or as-needed basis outside a clinical setting. Conventional devices are particularly unsuited for use during a user's regular activities at home, at work, while traveling, and during recreational and leisure activities.
Known pulmonary delivery devices that use electrohydrodynamic spraying also lack a sufficient volumetric flow rate to deliver a desired amount of certain therapeutic liquids during the inhalation of one to two breaths by a user. Attempts to increase the flow rate generally have resulted in even more bulky devices unsuitable for hand-held use. These delivery devices also are not generally capable of spraying liquids having a broad range of conductivities.
The commonly-owned U.S. Pat. No. 6,397,838 to Zimlich, Jr., et al., which is hereby incorporated by reference in its entirety, discloses a pulmonary aerosol delivery device that delivers an aerosolized liquid cloud having therapeutic properties to a user's lungs. The compact and convenient device includes a housing of such size that it can be held in a user's one hand with an exit opening in the housing for directing the aerosol to the user's mouth. The aerosolizing apparatus (i.e., EHD nozzle) includes a plurality of spray sites (i.e., tip ends) that cooperate with discharge electrodes and reference electrodes downstream respectively of the tip ends to result in an aerosolized spray from at least one tip end. The multiple spray sites can achieve larger dosages.
While U.S. Pat. No. 6,397,838 presents a significant advance over generally known aerosol delivery devices, we have recognized that opportunities exist for improvement. For instance, the EHD nozzle is to be pointed downwardly in order for each nozzle tip to dispense consistently. However, most users prefer to be upright when using the dispenser. Consequently, the dispensed aerosolized liquid had to be directed through a bend to the exit opening. Momentum of the aerosolized droplets tends to deposit some of the liquid onto the exit opening, reducing the effective dose delivered to the user. In addition, wetting of the interior of the EHD nozzle itself may degrade performance. Most if not all of the liquids dispensed by pulmonary delivery devices to some extent are conductive. Thus, wetting tends to dissipate the desired electric fields within the EHD nozzle, especially should a conduction path be formed between the discharge and reference electrodes. Wetting is mitigated to an extent by procedurally requiring the nozzle to be vertically oriented. Also, the interstitial reference electrodes reduced electrical arcing by greatly reducing a liquid conductive path between the nozzle tips and the reference electrodes. In addition, a current limiting resistor in the voltage producing circuit further controlled arcing. While these measures provided useful handheld dispensers, further enhancements are desirable to further eliminate wetting of the nozzle and to allow use of the dispenser in other orientations.
It is also desirable to have an EHD nozzle that produces a completely electrically neutralized aerosolized liquid. Having some droplets that retain a charge tends to compound wetting of the device or may limit the therapeutic effect (e.g., the mutual repulsion of charged particles may deposit the liquid prior to reaching the fullest extent of the lungs).
One approach that has been suggested is to create a corona of oppositely charged ions that mix with the charged aerosolized liquid droplets prior to leaving an inhaler device as taught by U.S. Pat. No. 4,801,086 to Noakes et al. An air passage is transverse to an aerosolizing chamber, with a positively charged metal capillary tube and a negatively charged discharge electrode on opposite sides of the chamber separated by the air passage. A Taylor Cone at the tube produces a ligament of aerosolized fluid that is attracted toward the discharge electrode. The discharge electrode produces a countering corona of positively charged ions that are directed toward the aerosolized particles, which upon interacting with the negatively charged particles neutralize the negative charge of the aerosolized particles prior to their leaving chamber. To protect the Taylor Cone to a certain extent from attack by the positively charged ions, a shield separates the tube from the air passage and discharge electrode. The shield has an orifice large enough to permit the passage of the aerosolized particles while being sufficiently small to prevent the corona of positively charged ions from passing therethrough to degrade the Taylor Cone formation at the tube.
However, it is believed that this approach to neutralizing the aerosolized liquid has several undesirable limitations. For example, the airflow is transverse to the opposing directions of the aerosolized liquid and ions, creating a turbulence that tends to hamper the neutralizing of the aerosolized liquid prior to exiting the device and tends to wet the interior of the inhaler device. In addition, it is further believed that the neutral shield will tend to be wetted by the aerosolized particles and the volume rate of aerosolized particles will be inconsistent due to the proximity of discharge ions. Thereby the dosage achieved may be inconsistent.
Consequently, a significant need exists for an improved EHD nozzle suitable for use in a portable pulmonary aerosol delivery device.